Senior guard Gabby D'Ercole scored three of the first four baskers and assisted on the other as Penfield (15-0) jumped out to an 8-2 lead.
D'Ercole, who finished with a team-high 17 points, hit back-to-back 3-pointers in the third quarter to extend Penfield's lead to 42-20.
Senior guard Lacey Coppage added 13 of her 15 points in the second half.
Senior forward Colleen Coon broke the school record with 20 rebounds, a record previously held by Alyssa Nugent in 2003.
Penfield held the Red Raiders without a field goal in the second quarter.
Junior forward Allyson DiMagno led the Red Raiders (9-7) with 20 points.
PENFIELD: Lacey Coppage 15, Gabby D'Ercole 17, Colleen Coon 4, Colleen Mahany 4, Sarah Tranelli 2, Megan Malloy 3, Monica Nesselbush 7, Colleen Lynd 2, Emma Morsch 0, Laura McNamara 2.
3-point goals: D'Ercole 3, Coppage.